Method and Apparatus for Non-Invasively Monitoring Analytes in Domesticated Animals

ABSTRACT

A device and method for noninvasively monitoring biofluids of an animal provides measuring physical parameters of an analyte with a device located within an oral cavity of the animal.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of co-pending of U.S. application Ser.No. 15/092,592, filed Apr. 6, 2016, and entitled METHOD AND APPARATUSFOR NON-INVASIVELY MONITORING ANALYTES IN DOMESTICATED ANIMALS, which inturn claims priority to and the benefit of U.S. Provisional ApplicationNo. 62/143,285, filed Apr. 6, 2015, each of which are incorporated byreferenced herein in their entirety for all purposes.

BACKGROUND

Millions of households throughout the world spend billions of dollarseach year on their pets. The American Pet Product ManufacturersAssociation (APPMA) regularly conducts a National Pet Owners Survey. Inits most recent survey for 2011-2012, the APPMA estimated that therewere 377.41 million pets in the United States, with 164.6 million or43.6% of them being cats (86.4M) or dogs (78.2M). The total spending onpets according to the survey was $50.96 billion and is expected to risenearly two billion dollars when its next survey is conducted. Of that,$25.18 billion was spent on supplies, over the counter medicine and vetcare. If we extrapolate those figure, roughly $10.98 billion of the$25.18 billion is spent on cats and dogs.

Dog diabetes is a relatively common dog health issue that all too oftengoes undetected until an emergency occurs. While only about 1 in 500dogs are diagnosed, some estimates show that as many as 1 in 100 dogshave diabetes. This means that about 782,000 registered dogs requireddiabetic treatment in the US.

The above-presented numbers indicate that blood glucose monitoring fordogs and cats has a solid market-based foundation.

Until recently, there have not been any methods and/or devicesspecifically designed to provide accurate non-invasive measurements ofthe blood glucose level in domesticated animals including dogs and cats.Devices developed for monitoring the human blood glucose level have beenused instead, with a slight modification of the peripheral members ofthe instruments and measurement procedures. From a technological pointof view, all existing methods for the blood glucose spot measurement orblood glucose curve building are either invasive (clinic blood test,clinic or home test using electro-chemical blood measuring devices likeOne-Touch U1tra™—relatively accurate; accuracy is affected by stress) orinaccurate (urine test).

All known approaches related to domesticated animals require collectingcertain amounts of some biological material, not necessarily a bloodsample, e.g., urine, saliva or tear liquid. Regardless of the kind ofbiological material used, each of these substances can be obtained bysampling that suggests a human interaction with the animal. Inparticular, a sample collecting container should be physically removedfrom contacting the animal for further analysis of its content (U.S.Pat. No. 5,139,023). A very few methods and methods-correspondingtechnologies can be named for obtaining information about the bloodglucose level in domesticated animals that hypothetically do not requiresampling. These techniques may include measuring the tissue's electricalconductivity, compressibility and thermal diffusivity successfullyapplied in the GlucoTrack™ product of Integrity Applications, Inc.,electromagnetic absorption constant (US Pat. Pub. No. 20130289370),absorption of laser/infrared radiation (U.S. Pat. No. 7,729,734),magneto-resonance absorption (U.S. Pat. No. 7,635,331), photo-acoustics(U.S. Pat. No. 5,941,821) and many others. All these measurement methodsare complicated by practically overall hairiness of the most ofdomesticated animals.

In-clinic stress may cause blood glucose to be elevated making itdifficult to determine the true blood glucose level

In order to get the most accurate readings, blood glucose monitoring isbest done under the pet's typical daily conditions. This is usually thehome environment where feeding, exercise, and stress levels are normal.Blood glucose values obtained in the clinic often do not accuratelyreflect the values of a typical day, complicating the regulationprocess.

The purpose of the present invention is presenting a method and at leastone conceptual design of an apparatus for accurate non-invasivemeasurement of the domesticated animal's blood glucose level causing nostress to the animal oblivious to the fact that the measurement is beingconducted.

BRIEF SUMMARY

The foregoing and other problems are overcome by methods and devices inaccordance with embodiments of this disclosure, wherein aspecially-shaped biofluids collector is combined with a sensory networkto obtain information about an analyte (e.g., blood glucose) level indomesticated animals by camouflaging the collector as an animal's toy.The device provides for a stress-free, non-invasive measurement of theanalyte and automatically controls the measurement process based onsignals from sensors responsible for identifying that the biofluidcollector is positioned in the designated space inside the animal's oralcavity. Measurements are allowed only upon confirmation that thebiofluids collector is positioned correctly inside the oral cavity ofthe animal. Different biological elements are used by sensors to gatherinformation about the blood glucose level, thereby allowing use ofsophisticated data mining analytical technique including neuralnetworking and genetic algorithms.

In one embodiment a method and device for measuring at least one analytelevel in an animal is disclosed, wherein the device may comprise a bodyhaving a predetermined shape and size at least partially insertable intoan oral cavity of the animal so as to expose a surface of the body tobiofluids in the oral cavity, and an analyte measuring system housedwith the body. The analyte measuring system may include a biosensingunit for measuring at least one analyte in biofluids present in the oralcavity of the animal, and a signal output component operably coupled tothe biosensor and configured to generate at least one output signal inresponse to activation of the biosensing unit.

In another embodiment, the biosensing unit may be comprised of one ormore sensors indicating a desired positioning of the body at leastpartially within the oral cavity of the animal. A computing means, suchas a circuit or microprocessor, may activate the biosensing unit toacquire analyte sensing data only while the body is in the desireposition in the oral cavity. For example, if the toy is dropped by theanimal, measurements would be halted until the toy is properlyrepositioned in the animal's mouth.

In yet another embodiment, the biosensing unit may comprise a BFC, ameans for transporting the biofluids (e.g., capillary conduits or poresin the toy surface, etc.) from the oral cavity to the BFC, and a sensorynetwork comprised of a plurality of the sensors disposed around and/orwithin the BFC.

In another aspect, the biosensing unit may include a biofluid container(BFC), and one or more capillary conduits connected on a first end tothe BFC and having a second end positioned at, or near, the surface ofthe chew toy so as to permit biofluids to be collected and transportedfrom the animal's oral cavity to the BFC. One or more sensors may beconfigured to be in fluid connection with the transported to andcollected at the BFC. The sensors may be any type of sensor providingmeaningful information regarding, for example, the volume of collectedbiofluid(s), or physical variables from which the position of the toyand/or the analyte concentrations may be determined. For example, thesensor(s) may detect a set of physical variables functionally dependenton glucose concentration in the biofluids, and in response outputphysical variable signals. From the physical variable signals, acomputing unit that may be implemented as a circuit, processor, or othermeans, housed within the toy, or in remote wireless communication withbiosensing unit, may determine the glucose level. Such sensors mayinclude electrochemical sensors, photoelectric sensors, infraredsensors, acoustic sensors and electromagnetic sensors, etc. Thecomputing unit may operate to condition the physical variable signals toprovide stable data and to estimate variables for determining the atleast one analyte level. The estimating variables may possessunambiguous relationship with the at least one analyte level, makingthem useful as components of a vector input of a biosensing unitcalibration function. The computing unit may be configured to build thecalibration function and calculate the analyte concentration in thebiofluids. Those of skill in the art will readily appreciate that any ofthe aforementioned functions may be performed by a computing unitcontained within the toy or remotely located, or divided between suchcomputing units.

These and other aspects of this disclosure, as well as the methods ofoperation and functions of the related elements of structure and thecombination of parts and economies of manufacture, will become moreapparent upon consideration of the following description and theappended claims with reference to the accompanying drawings, all ofwhich form a part of this specification, wherein like reference numeralsdesignate corresponding parts in the various figures. It is to beexpressly understood, however, that the drawings are for the purpose ofillustration and description only and are not a limitation of theinvention. In addition, it should be appreciated that structuralfeatures shown or described in any one embodiment herein can be used inother embodiments as well.

Another embodiment of the present invention may provide a method formeasuring at least one analyte level in biofluids of an animal,comprising the steps of: disposing an analyte collection and measurementdevice in proximity to an animal; determining when the analytecollection and measurement device is potentially exposed to biofluids ofthe animal while the animal is relaxed; collecting biofluids in responseto the step of determining; measuring at least one analyte in collectedbiofluids of the animal with a biosensing unit; and generating an outputsignal in response to measurement by the biosensing unit.

The method may further comprise wirelessly transmitting the outputsignal from the analyte collection and measurement device. The step ofdetermining may include sensing the presence of the analyte collectionand measurement device within the oral cavity of the animal and sensingmotion of the analyte collection and measurement device. The step ofmeasuring comprises detecting a set of physical variables functionallydependent on glucose concentration in the bio fluids and computing fromthe step of detecting a glucose value in response to the physicalvariable signals. The step of computing may include creating estimatingvariables, building a calibration function and calculating values of ananalyte concentration in the bio fluids.

BRIEF DESCRIPTION OF THE FIGURES

The illustrations of the accompanying drawings are not necessarily toscale, emphasis instead being placed upon illustrating the principles ofthe examples, wherein:

FIG. 1 is a flow chart of a method in in accordance with an exemplaryembodiment of the invention;

FIG. 2 is an illustration of an exemplary functional block diagram of ananalyte measuring device;

FIG. 3 is a schematic illustration of a chew toy embodiment of ananalyte measuring device in accordance with the invention; and

FIG. 4 is an illustration of an analyte measuring device in a possibledesired position within a dog's oral cavity.

DETAILED DESCRIPTION

Reference is now made to the figures, depicting implementations ofmethods and devices for measuring an analyte, such as blood glucoselevel, in domesticated animals. In the detailed descriptions ofembodiments that follow, glucose is measured through use of abone-shaped toy housing 10 for an analyte measuring system 12 sensingthe animal's biofluid 14 (i.e., saliva.) However, the descriptions arein no way intended to limit the scope of the invention to thatparticular analyte or biofluid (e.g., other biofluids could includemucus, blood, breath, etc.), or to the specific configurations ofcomponents described. A bone shaped toy housing 10 assists in properlypositioning the sensing portion of the analyte measuring system 12properly in the animal's oral cavity 16, but other shapes conceivablyalso accomplish this goal. Similarly, the signal output device 18 in adescribed embodiment comprises a wireless transmitter for transmittingsensed physical variables and/or computed analyte levels to a remotereceiver 20, however those of skill in the art would readily appreciatealternative analyte read-out mechanisms, such as an output port on thedevice that may be connected and disconnected to a remote computingsystem.

The presented novel solution to measuring blood glucose level indomesticated animals is based on the following operating principlesand/or components:

-   -   1. A specially-designed BFC 22 capable of accumulating the        biofluids 14 without being noticed by the animal;    -   2. a multi-channel sensory network 24 for simultaneous        measurement of a set of physical variables        functionally-dependent on the glucose concentration in the        biofluid 14;    -   3. at least two of the glucose-relating physical variables        demonstrate orthogonally toward environmental disturbances to        the process of measurement;    -   4. at least two of the glucose-relating physical variables are        captured by interacting with at least two different body's        biological elements;    -   5. wireless control of the measurement process and measured data        outputting; and    -   6. self or forced cleaning of the biological fluid collector        when the measurement system is idle.

The first principle ensures an accurate measurement of the blood glucoselevel by eliminating the development of the so-called “stress sugar”during the sample taking.

The second and the third principles provide for an effective applicationof methods of regression analysis and optimization and artificialintelligence (neural networking, genetic algorithms, etc.) for designingan optimal measurement algorithm

The fifth and the sixth principles support the non-invasive andundistinguishable nature of the proposed blood glucose measurement whichis crucially important once the measurement is applied to animals.

With reference to FIG. 1, a measurement process 90 may include asequence of the following steps that will be described below in detail.

The process 90 begins at step 100, where the analyte measuring system 12is on standby and receiving signals indicating positioning of the toyfrom one or more continuously sensing sensors, such as a vibrationsignal from a vibration sensor 30 and for an electromagnetic signal froma measurement coil 32. Both the vibration sensor 30 and the measurementcoil 32 may be incorporated in the body of the analyte measuring system12.

In step 110, the analyte measuring system 12 may be activated,initiating the measuring procedure, when the vibration signal coupledwith the electromagnetic signal indicate that the BFC 22 is positionedin the predetermined zone in the animal's oral cavity 16. While properpositioning is not detected, continuous monitoring of the sensor 30, 32continues but no analyte-level related sensor measurement data isacquired. As noted above, correct positioning of the BFC 22 may beassured by the special bone-like shape of the toy housing 10. When theanimal clinches to the toy 10 inside the oral cavity 16, it creates aspecific spectral response that can be captured by a vibration sensor30, e.g., accelerometer (such as described on the www.ultimompd.comwebsite, although unrelated to the glucose measurement). Then, thevibration signal may decay, indicating the fact that the toy 10 is notmoving. At the same time, an electromagnetic sensor, by measuring theimpedance of the hard pallet in a certain frequency range, may indicatethat the toy 10 is positioned within the limits of a distance betweenthe center of mass of the toy 10 and the animal's hard pallet. Together,these two signals may identify the moment when the toy 10 is in theposition suitable for the measurement. Additionally or alternative, aplurality of pressure sensors (not shown) may be used also, disposedabout the circumference of the toy 10 and spread along a certain lengthon the toy 10.

In step 120, monitoring may be activated based on the amount of thesaliva 14 in the BFC 22 by using signals relating to the amount ofaccumulated saliva, as determined from one or more sensors 34. Theamount of saliva may be used to trigger the measuring processing. Datacollection by the sensory network 24 will depend on a sufficient amountof biofluid 14 (i.e., saliva) is accumulated. An animal may take anddrop the toy 10 as many times as it wants without affecting the qualityof the measurement. There are a variety of methods for measuring volumeor mass of liquid material in the BFC 22 that may be used. For example,optical (transparency of the medium is evaluated), ultrasound (“Time offlight” paradigm can be used, or wave's phase shift captured at thesides of the container) capacitance-based methods, floating levelsensors, and many more.

In step 130, signal capture is initiated from each sensor 34 of thesensory network 24 located inside and or in the vicinity the BFC 22. Thesignals capturing sequence may be controlled by the amount of salivarequired for each member of the sensory network 24 to generate responsessatisfying the requirements of the high quality signal processing.

In step 140, signals are processed from the sensory network 24.

In step 150, a vector is sent of glucose-sensitive signals obtained fromthe sensory network 24 a data processing module 36 for data processingand storage, generation of the estimating variables further used by amathematical procedure for outputting the desired value of the glucoseconcentration in the animal's biofluid 14

In step 160, the analyte (i.e., blood glucose, etc.) level may becalculated from the measured signals.

In step 170, a determination is made whether sufficient data has beencollected to complete the measurement and determine the analyte level.If not, the measuring and calculating continue. If the measurement hascompleted, the analyte level may be output (step 180) and the processreturns to the determination at step 110 whether additionalanalyte-level related sensor 24 data acquisition may proceed. If theanimal drops the toy 10, or otherwise misplaces the BFC 22 from thedesired position (e.g., position 40 in FIG. 4) in the oral cavity 16,the measuring process is interrupted, and the data acquired to thatpoint is stored for aggregation with future acquired data once theconditions of step 110 are satisfied.

In step 180, the measuring process may be completed and “measurementcompleted” confirmation signals collected from each measuringinformation channel of the analyte measuring system 12, and theresulting measured value(s) of the blood glucose output to recipients.

A functional block-diagram of an embodiment of the analyte measuringsystem 12 and toy housing 10 facilitating the above-describedmeasurement process is shown in FIG. 2. According to this diagram, theBFC 22 (shown with its housing removed for clarity) collects saliva 14via a system or systems of capillary-type conduits 38. Saliva 14 isaccumulated in a fluids sample container 40. One or more sensors of thesensory network 24 may be arranged around or inside the same BFC 22. Thesensors in each sensory network 24 could be based on proven glucosemeasuring technologies, such as disclosed in U.S. Pat. Nos. 6,954,462,6,882,940, 6,405,069, 6,377,828 and 6,309,352, the contents of each ofwhich are hereby incorporated by reference. The sensors of sensorynetwork 24 provides responses of the highest possible accuracy andprecision because the sampled saliva is being accumulated in the BFC 22under the absence of disturbing factors that usually accompanymeasurements performed on living organisms. This near laboratory degreeof accuracy and precision of measurements is a substantial advantage ofthe present method and apparatus. Regardless of which physical propertyof the tissue or body fluid is measured in order to monitor the glucoseconcentration in a living mammal organism, having this specimen isolatedfrom disturbing factors produced or experienced by a normallyfunctioning organism, improves the accuracy and precision ofmeasurements and creates an opportunity for a simultaneous use of avariety of sensors which responses link the glucose concentration tomeasurable physical properties of the fluid, e.g., dielectric constant,compressibility, thermal diffusivity, and electromagnetic absorptionconstant, etc. The vector of signals from the sensory network 24 may besent to a signal conditioning computing unit 42, where each component ofthe vector is treated in accordance with the particular properties ofthe sensor generating the respective signal(s).

The conditioned signal (v) 44 from a vibration sensor 46 and aconditioned signal (u) 48 from an electromagnetic sensor 50, the eachdelivering information about the position and the positional stabilityof the toy 10 in the animal's oral cavity 16, are used in accordancewith the measurement method for automatically controlling the method'ssequence of operations. Additionally, the electromagnetic sensor 50 maybe used for measuring the blood glucose level by evaluating the compleximpedance of the electromagnetic coupling between the measuring coil andthe tissue of the animal's hard palate.

Finally, the conditioned vector-output of the sensory network 24 may goto a generator of estimating variables 52, which is shown as a distinctfunctional block but which could be a function performed by computingunit 42 or a remote computing system. This functional block takes theconditioned signal or signals from some group of sensors and convertsthen into a variable that carries information about the glucose leveland allows its further conversion into the glucose concentration by ablood glucose concentration calculator block 54 (which also could beimplemented within computing unit 42, or at a remote computing system.)The output of the blood glucose concentration calculator block 54 may bewirelessly transferred to receiver 20, where an additional mathematicalanalysis of the gathered blood glucose level readings can be performed.

Various implementations of the proposed system are possible withdifferent functional roles playing by the apparatus' analog and digitalhardware within the logic of the proposed algorithm and functional blockdiagram of the apparatus. For example, the estimating variables can begenerated within the sensory network 24 and the glucose concentration inblood can be calculated after the vector of estimating variables hasbeen wirelessly transferred to a remote blood glucose calculator.

A schematic illustration of the bone-shaped toy housing 10 and ananalyte measuring system 12 is shown with greater detail in FIG. 3. Inthis embodiment, analyte measuring system 12 is comprised of theregistries of capillary-type conduits 38 for capturing and directing thebiofluids 14 into the BFC 22 as indicated by arrow 56 . Thecapillary-type conduits 38 and the sensory network 24 are assembledaround the BFC 22 so the measurements are possible at any angularposition of the BFC 22 rotating around the axis “y” in a coordinatesystem xyz shown. As an example of the invention application tomeasuring the blood glucose level in dogs, the outline of the BFC toyhousing 10 resembles a bone which curves provide for guiding the BFC 22into a designated position in the oral cavity 16 of the particular dog.An illustration of the conceptual idea of how the BFC 22 isself-positioned in the dog's oral cavityl6 is given in FIG. 4. When ananimal, e.g., a dog, plays with the bone-looking toy 10, the animal willnot notice that the measurement will be conducted each time when the“bone” will be taken by the animal into the animal's mouth andautomatically positions itself inside the mouth at the designated place.The plurality of sensors capturing different physical variables fromdifferent biological substances of the animal creates a sufficientvector of informative variables that substantiate accurate measurementof the animal blood glucose concentration in real time.

Based on the provided description of the measurement's algorithm and theapparatus implementing the measurement method, one can build a devicefor the accurate, non-invasive blood glucose level measurement indomesticated animals without causing any stress to the animal that isthe main source of error in all the existing measurement methods.

As used above, the terms “comprise,” “include,” and/or plural forms ofeach are open ended and include the listed parts and can includeadditional parts that are not listed. “And/or” is open ended andincludes one or more of the listed parts and combinations of the listedparts. “Terms” and “coefficients” have been used interchangeably in thedescription above.

One skilled in the art will realize the invention may be embodied inother specific forms without departing from the spirit or essentialcharacteristics thereof. The foregoing embodiments are therefore to beconsidered in all respects illustrative rather than limiting of theinvention described herein. Scope of the invention is thus indicated bythe appended claims, rather than by the foregoing description, and allchanges that come within the meaning and range of equivalency of theclaims are therefore intended to be embraced therein.

What is claimed is:
 1. A device for measuring at least one analyte level in an animal, the device comprising: a body having a predetermined shape and size at least partially insertable into an oral cavity of the animal so as to expose a surface of the body to biofluids in the oral cavity; an analyte measuring system housed with the body, including a biosensing unit for measuring at least one analyte in biofluids present in the oral cavity of the animal, and a signal output component operably coupled to the biosensor and configured to generate at least one output signal in response to activation of the biosensing unit.
 2. The device of claim 1, wherein the analyte comprises glucose.
 3. The device of claim 1, wherein the signal output component comprises a wireless transmitter.
 4. The device of claim 2, further comprising a remote receiver wirelessly receiving the at least one output signal.
 5. The device of claim 1, wherein the biofluids comprise at least one of saliva, mucus, blood or breath.
 6. The device of claim 1, wherein the biosensing unit further comprises: at least one sensor indicating a desired positioning of the body at least partially within the oral cavity of the animal; and a computing means for activating the biosensing unit to acquire analyte sensing data while the body is in the desire position in the oral cavity.
 7. The device of claim 1, wherein the biosensing unit comprises: a biofluid container; at least one capillary conduit connected on a first end to the biofluid container and a second end disposed at or near the surface of the chew toy so as to enable collection and transport of biofluids from the oral cavity of the animal to the biofluid container; and at least one analyte sensor in fluid connection with the biofluids transported to the biofluid container.
 8. The device of claim 7, wherein: the at least one analyte sensor comprises a plurality of sensors detecting a set of physical variables functionally dependent on glucose concentration in the biofluids and outputting physical variable signals; the biosensing unit further comprises a computing means in communication with the plurality of sensors and determining a glucose value in response to the physical variable signals.
 9. The device of claim 1, wherein the biosensing unit comprises: a biofluid container; and means for transporting biofluid from the oral cavity of the animal to the biofluid container; and a sensory network comprised of a plurality of sensors disposed at least at one position around and within the biofluid container.
 10. The device of claim 9, wherein the plurality of sensors are selected from the group consisting of electrochemical sensors, photoelectric sensors, infrared sensors, acoustic sensors and electromagnetic sensors.
 11. The device of claim 1, wherein the biosensing unit comprises: a sensory network including a plurality of sensors detecting a set of physical variables functionally dependent on the analyte concentration in the biofluids and outputting physical variable signals; a computing means for conditioning the physical variable signals to provide stable data and estimating variables for determining the at least one analyte level.
 12. The device of claim 11, wherein the estimating variables possess unambiguous relationship with the at least one analyte level, such that the estimating variables may be used as components of a vector input of a biosensing unit calibration function.
 13. The device of claim 11, further comprising a remote computing system, wherein: the signal output component wireless delivers the output physical variable signal values of the sensory network to the remote computing system; and the remote computing system is configured to create estimating variables, build the calibration function and calculate values of the analyte concentration in the biofluids of the animal.
 14. The device of claim 11, wherein the computing means is configured to create estimating variables, build the calibration function and calculate values of the analyte concentration in the biofluids of the animal.
 15. The device of claim 1, wherein the predetermined shape comprises the shape of a bone.
 16. A method for measuring at least one analyte level in biofluids of an animal, comprising the steps of: disposing an analyte collection and measurement device in proximity to an animal; determining when the analyte collection and measurement device is potentially exposed to biofluids of the animal while the animal is relaxed; collecting biofluids in response to the step of determining; measuring at least one analyte in collected biofluids of the animal with a biosensing unit; and generating an output signal in response to measurement by the biosensing unit.
 17. The method of claim 16, further comprising wirelessly transmitting the output signal from the analyte collection and measurement device.
 18. The method of claim 16, wherein the step of determining includes sensing the presence of the analyte collection and measurement device within the oral cavity of the animal and sensing motion of the analyte collection and measurement device.
 19. The method of claim 16, wherein the step of measuring comprises detecting a set of physical variables functionally dependent on glucose concentration in the bio fluids and computing from the step of detecting a glucose value in response to the physical variable signals.
 20. The method of claim 19, wherein the step of computing includes creating estimating variables, building a calibration function and calculating values of an analyte concentration in the bio fluids. 